Toluene → HCID 178477537, Verbindung

A solution of triphenylphosphine (21.55 g, 82 mmol) and (R)—N-(2-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-2-hydroxypropyl)-4-nitrobenzenesulfonamide (37.56 g, 69 mmol) in 510 ml THF was cooled to 4° C. A solution of diethyl azodicarboxylate in toluene (40% by weight, 38.8 g, 89 mmol) was added in a dropwise while maintaining the temperature below 10° C. The cooling bath was removed and the rm was stirred at rt for 1 h. The reaction mixture was diluted with approx. 1000 ml toluene and THF was removed by evaporation at the rotavap. The resulting toluene solution of crude product was pre-purified on a silca gel column by eluting with hexanes/5-17% EtOAc. Purest fractions were combined, evaporated and crystallized from TBME/hexane to yield 29.2 g of the title compound as white crystals. HPLC: RtH11=2.546 min; ESIMS: 530, 532 [(M+H)+, 1 Br]; 1H-NMR (400 MHz, CDCl3): 8.40 (d, 2H), 8.19 (d, 2H), 7.39 (d, 1H), 3.14 (s, 1H), 3.02 (s, 1H), 2.01 (s, 3H) 1.03-0.83 (m, 15H); α[D]-35.7° (c=0.97, DCM).

1. temperaturewhile maintaining the temperature below 10° C
2. customThe cooling bath was removed
3. additionThe reaction mixture was diluted with approx. 1000 ml toluene and THF
4. customwas removed by evaporation at the rotavap
5. customThe resulting toluene solution of crude product was pre-purified on a silca gel column
6. washby eluting with hexanes/5-17% EtOAc
7. customevaporated
8. customcrystallized from TBME/hexane

ORD-Eintrag

ord-9846bd3fbd564261b69dbac3c205bcb8

Quelldatensatz

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08637508B2